The goal of this proposal is the understanding of the relationship between those ganetic mechanisms which regulate and expression of the terminal phenotype in the developing animal and those which regulate aging of the terminal phenotype in the aging animal. The experiental material is cartilage tissue. Changes in the molecular composition of the extracellular matrix occurring with age in vivo and in vitro will be studied at the levels of transcription, post-transcription and translation. Aging cartilage-characteristic Type IV proteoglycans and Type II collagen. Cartilage is a unique tissue for studying aging, for it can be reared in vitro under distinct conditions: 1) as dispersed monolayer or suspension of replicating cells; and 2) as pellet or organ cultures of low or non-replicating cells. Thus, the contribution of cell replication for aging of cartilage cells in these experimental models can be analyzed. To determine whether aging is a genetically programmed, temporal sequence of biosynthetic changes, or whether it is imposed by reversible microenviriomental cues, cartilage cells from young and old animals will be reared under the same culture conditions; the structure of proteoglycans and collagen newly-synthesized by these cells and the mechanisms of regulation will be compared. The results of the proposed experiments may suggest ways to modify the chondrogenic terminal phenotype in terms of biosynthetic program, and possibly suggest rational therapies for treating some pathologies of the cartilage tissue, particularly those associated with aging.